PDE5 inhibition improves acquisition processes after learning via a central mechanism.

In previous studies, we have shown that phosphodiesterase type 5 inhibitors (PDE5-Is) can improve early consolidation of object memory. These conclusions were based on the timing of drug administration relative to the learning trial (i.e. before or after). However, there are very little pharmacological data available about the pharmacokinetic profile of orally administered PDE5-Is in the rat. Furthermore, there is still debate whether these effects are achieved via central or peripheral mechanisms and if acquisition processes are improved. In the current study, we tested the effects of the PDE5-I vardenafil in a cholinergic-deficit model and compared the effects after intracerebroventricular (ICV) versus oral (PO) administration. We found that PO vardenafil restored a scopolamine-induced memory impairment when dosed within 2 min after the learning trial while ICV vardenafil was able to restore memory when injected within 4 min after learning. Because the test trial was within 10 min after the learning trial, this suggests that these effects on object memory are related to acquisition processes that may still be ongoing in a time window after the learning trial. To further elucidate the extent of this acquisition window, we investigated the pharmacokinetic profile of vardenafil after PO administration where it was detected within 4 min post-dose. Taken together, our data suggest that PDE5 is involved in acquisition processes, which may linger for at least 4-6 min after learning. Further studies are needed to exclude that these effects could also be explained on basis of an effect on early consolidation processes. Additionally, the effectiveness of ICV-administered vardenafil provides further experimental evidence that PDE5-Is improve memory via a central mechanism.

[A fresh look at psychiatric disorders]. / Een veranderende kijk op psychiatrische stoornissen.

BACKGROUND: The a-theoretical approach to psychiatric disorders, introduced via dsm iii, has had a tremendous impact. It has stimulated a large body of research, facilitated by the concurrent development of new techniques in genetics, neuro-imaging and neuropsychology. However, the research results of the last twenty years or so have cast doubt on the validity of the clinical categories set out in dsm iii. AIM: To develop a new view on developmental pathways in psychopathology, clinical assessment and scientifically acceptable classification. METHOD: In this article we review the state of the art with regard to underlying endophenotypes at the level of brain and neurotransmitter functioning and neuropsychology and we consider the effect of social determinants on the developments of psychopathology. RESULTS: Our results show that neither genotypes and endophenotypes, nor brain mechanism, nor neuropsychological deviances have a one-to-one correlation with clinical categories as defined in even the dsm 5. CONCLUSION: dsm-5 provides a range of possibilities for classifying psychiatric disorders at symptom level. But these categories seem to be less distinct than was at first assumed. Recent research has shown that there is a great deal of overlap at the genetic, epigenetic and endophenotype level. This calls for more emphasis on individual assessment and diagnostics in both clinical practice and scientific research. More attention needs to be given to the dimensions of emotion and behavior, vulnerability and resilience. This type of approach, involving genotypes, endophenotypes, epigenetics and brain functioning, could help to elucidate the interaction between these various levels and/or explain the underlying mechanisms of psychiatric disorders.

[The challenge of staging developmental disorders]. / Stagering: een ontwikkelingspuzzel.

BACKGROUND: On the basis of our current knowledge, developmental disorders can be divided into the following stages: stage 0: normal variation, stage 1: simple disorder of moderate severity, stage 2: complicating co-morbidity and/or harmful background circumstances, and stage 3: serious disorder with harmful background circumstances. AIM: To describe the current views on prognostic aspects of staging from a developmental perspective. METHOD: The study is based on a critical review of the relevant literature. RESULTS: The current division into stages is still insufficiently predictive, partly because development is a flexible process with risks, chances and second chances. All psychiatric disorders are in essence developmental disorders that arise in the course of development as a result of the interaction between predisposition and background circumstances. As from the very first meiosis the hereditary predisposition is subject to influences in the womb environment. The forming of networks in the brain, the distribution of neurotransmitters and the neurological profile are influenced by the genetic potential for chances and risks and are all a result of interactions. This complicated developmental history raises questions about the specificity of current clinical syndromes. CONCLUSION: In time there is likely to be a much more accurate staging system. This will come about if, as a result of the analysis of large pooled databases, it becomes possible to make a better assessment of the relative risks of genetic configurations, brain connections, stress regulation in the brain, neuropsychological profiles and behavioural and emotional forms of expression in the light of the interactions that occur with the aforementioned background circumstances.

Ultrasound demonstration of a superior mesenteric artery aneurysm in a patient with Ehlers-Danlos syndrome.

A large aneurysm of the superior mesenteric artery was the presumed cause of abdominal pain in an 11-year-old girl with Ehlers-Danlos syndrome. This aneurysm was readily identified by ultrasonography, suggesting that this method could be the diagnostic technique of choice in this disorder.

[Dangers of batteries]. / Dangers des piles.

During the years 1982-1987 the Dutch Poison Control Centre was consulted 333 times about batteries. From these inquiries 281 concerned ingestion of a battery. In 52 cases there had been contact with (the contents of) a battery either with the skin, or the eyes or mucus membranes. The obtained data are compared with data in literature. In literature it is found that after ingestion in about 90% of the cases no symptoms occur. Problems develop when the battery is lodging somewhere in the gastrointestinal tract. Perforation is the most dangerous complication. Sometimes a battery can be found in the nose or in the external auditory canal of a child. As a result of a prolonged stay on one place, severe tissue damage may develop. When a battery is ruptured an intoxication due to metals might be expected we never observed it sofar. For locating the exact position of a battery in the gastrointestinal tract an X-ray photograph can be made. The therapies installed differ from waiting for the battery to come out with the stools to operative intervention. We suggest that when a patient has symptoms, medical intervention is required immediately; in the other case one can wait. When a battery is found in the nose or the ear immediate removal is required.